The human interleukin-2 receptor is being studied to understand critical components of the T cell immune response in normal and neoplastic cells. Following T-cell activation, IL-2 and IL-2 receptors are induced; the magnitude and duration of the T-cell immune response is controlled by the amount of IL-2 produced, the levels of receptors expressed, and the time course of these events. Three chains of the IL-2 receptor exist, IL- 2Ralpha, IL-2Rbeta, and gamma-c with IL-2Ralpha and IL-2Rbeta being significantly regulated at the level of transcription. The types of signals induced by IL-2 and the mechanism of regulating IL-2Ralpha and IL- 2Rbeta, both of which are induced by antigen as well as IL-2, are the main interests of this project. In the past year, the group has (1) Reported the existence of a new enhancer in the IL-2Ralpha 5' regulatory region containing an essential binding site for Elf-1, an Ets family protein. We demonstrate that Elf-1 physically associates with NF-kappaB p50, c-Rel, HMG-I(Y), and TFIIB, suggesting a functional interaction between this enhancer element, the basal transcription machinery (via TFIIB) and the previously identified upstream enhancer (which binds p50 and c-Rel). A binding site selection analysis has provided common themes for the activation of IL-2Ralpha and other T-cell activation genes who transcription is regulated by Elf-1. (2) Major progress has been made in analyzing the STAT proteins (signa transducers and activators of transcription) induced by IL-2. IL-2 was shown to induce Stat5 in fresh peripheral blood lymphocytes (PBL) and both Stat3 and Stat5 in PBL preactivated with phytohemagglutinin. Moreover, IL-7 and IL-15 activate the same STAT proteins as IL-2, a finding explained based on the presence of similar motifs in the cytoplasmic domains of both IL-2Rbeta and IL-7R. Human Stat5 was cloned and it was found that two proteins (>90% amino acid identity) are encoded by two closely related genes on chromosome 17. (3) A new Stat protein has putatively been cloned. (4) Putative Stat protein binding sites have been identified in the 5' regulatory regions of the IL- 2Ralpha and IL-2Rbeta genes, providing a molecular basis for IL-2 upregulation of these genes. Overall, these findings extend our understanding of IL-2 receptor gene regulation as well as other T-cell activation genes regulated by Elf-1 or Stat5.